Journal article
Insulin-Like Growth Factor-1 Receptor Expression and Disease Recurrence and Survival in Patients with Resected Pancreatic Ductal Adenocarcinoma
Cancer epidemiology, biomarkers & prevention, Vol.29(8), pp.1586-1595
08/01/2020
DOI: 10.1158/1055-9965.EPI-19-1315
PMCID: PMC7415636
PMID: 32467349
Abstract
Background: Insulin-like growth factor-1 receptor (IGF1R) signaling is important in pancreatic ductal adenocarcinoma (PDAC) biology, but little is known regarding IGF1R expression and patient characteristics and outcomes.
Methods: In 365 patients with resected PDAC, we evaluated IGF1R protein expression using IHC on whole-slide sections and IGF1R genomic status using next-generation sequencing. Associations of IGF1R expression, measured by H-scores incorporating staining intensity and proportion of positive tumor cells, with disease-free survival (DFS) and overall survival (OS) were evaluated in 317 and 321 patients, respectively, using Cox regression adjusting for known prognostic factors.
Results: Higher IGF1R expression in tumor cells was associated with worse DFS comparing highest versus lowest expression tertiles [median DFS, 10.8 vs. 16.1 months; adjusted hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.24-2.44; P-trend = 0.002] and worse OS (median OS, 17.4 vs. 25.8 months; HR, 1.39; 95% CI, 1.00-1.92; P-trend = 0.046). The association between high IGF1R expression and reduced DFS was identified primarily among patients with a preoperative body mass index >= 25 kg/m(2) (HR, 4.27; 95% CI, 2.03-8.96, comparing extreme tertiles; P-interaction = 0.032). KRAS-mutant tumors had greater IGF1R expression, and IGF1R expression in tumor epithelium was inversely correlated with that in stromal cells. Mutations in IGF1R were infrequent, and no overt loss-of-function alterations were identified. Higher IGF1R expression was modestly associated with higher gene copy number (Pearson correlation coefficient = 0.26, P < 0.001).
Conclusions: Higher IGF1R protein expression was associated with worse patient outcomes in resected PDAC.
Impact: IGF1R expression in PDAC represents a potential biomarker to guide patient selection for more aggressive, multidrug regimens in the adjuvant setting.
Details
- Title: Subtitle
- Insulin-Like Growth Factor-1 Receptor Expression and Disease Recurrence and Survival in Patients with Resected Pancreatic Ductal Adenocarcinoma
- Creators
- Chunxia Du - Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.Annacarolina Silva - Dana Farber Canc Inst, Dept Oncol Pathol, Boston, MA 02115 USAVicente Morales-Oyarvide - The University of Texas Southwestern Medical CenterAndressa Dias Costa - Dana-Farber Cancer InstituteMargaret M. Kozak - Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California.Richard F. Dunne - University of Rochester Medical CenterDouglas A. Rubinson - Dana-Farber Cancer InstituteKimberly Perez - Dana-Farber Cancer InstituteYohei Masugi - Keio UniversityTsuyoshi Hamada - Dana-Farber Cancer InstituteLauren K. Brais - Dana-Farber Cancer InstituteChen Yuan - Dana-Farber Cancer InstituteAna Babic - Dana-Farber Cancer InstituteMatthew D. Ducar - Dana-Farber Cancer InstituteAaron R. Thorner - Dana-Farber Cancer InstituteAndrew Aguirre - Dana-Farber Cancer InstituteMatthew H. Kulke - Boston Medical CenterKimmie Ng - Dana-Farber Cancer InstituteThomas E. Clancy - Brigham and Women's HospitalJennifer J. Findeis-Hosey - University of Rochester Medical CenterDaniel T. Chang - Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California.Jason L. Hornick - Brigham and Women's HospitalCharles S. Fuchs - Yale Cancer Center, Smilow Cancer Hospital and Yale School of Medicine, New Haven, Connecticut.Shuji Ogino - Dana-Farber Cancer InstituteAlbert C. Koong - The University of Texas MD Anderson Cancer CenterAram F. Hezel - Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California.Brian M. Wolpin - Dana-Farber Cancer InstituteJonathan A. Nowak - Harvard University
- Resource Type
- Journal article
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.29(8), pp.1586-1595
- Publisher
- Amer Assoc Cancer Research
- DOI
- 10.1158/1055-9965.EPI-19-1315
- PMID
- 32467349
- PMCID
- PMC7415636
- ISSN
- 1055-9965
- eISSN
- 1538-7755
- Number of pages
- 10
- Grant note
- Promises for Purple MyBlueDots Fund Noble Effort Fund Wexler Family Fund R35 CA197735 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U01 CA210171; P50 CA127003 / NIH/NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Lustgarten Foundation Pancreatic Cancer Action Network K07 CA148894 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Hale Center for Pancreatic Cancer Research
- Language
- English
- Date published
- 08/01/2020
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984313090102771
Metrics
13 Record Views